Department of Molecular Pharmacology, Division of Engineering and Medical Science, Brown University, Providence, RI 02912, USA.
Proc Natl Acad Sci U S A. 2010 May 4;107(18):8201-6. doi: 10.1073/pnas.1002292107. Epub 2010 Apr 19.
Although other methods exist for monitoring gastrointestinal motility and contractility, this study exclusively provides direct and quantitative measurements of the forces experienced by an orally ingested pill. We report motive forces and torques calculated from real-time, in vivo measurements of the movement of a magnetic pill in the stomachs of fasted and fed humans. Three-dimensional net force and two-dimensional net torque vectors as a function of time data during gastric residence are evaluated using instantaneous translational and rotational position data. Additionally, the net force calculations described can be applied to high-resolution pill tracking acquired by any modality. The fraction of time pills experience ranges of forces and torques are analyzed and correlate with the physiological phases of gastric digestion. We also report the maximum forces and torques experienced in vivo by pills as a quantitative measure of the amount of force pills experience during the muscular contractions leading to gastric emptying. Results calculated from human data are compared with small and large animal models with a translational research focus. The reported magnitude and direction of gastric forces experienced by pills in healthy stomachs serves as a baseline for comparison with pathophysiological states. Of clinical significance, the directionality associated with force vector data may be useful in determining the muscle groups associated with gastrointestinal dysmotility. Additionally, the quantitative comparison between human and animal models improves insight into comparative gastric contractility that will aid rational pill design and provide a quantitative framework for interpreting gastroretentive oral formulation test results.
虽然存在其他监测胃肠道动力和收缩性的方法,但本研究专门提供了口服药丸所经历的力的直接和定量测量。我们报告了从磁性药丸在禁食和进食的人体胃中的实时体内运动测量中计算出的主动力和扭矩。使用瞬时平移和旋转位置数据评估胃停留期间的三维净力和二维净扭矩矢量随时间的数据。此外,所描述的净力计算可应用于任何模态获得的高分辨率药丸跟踪。分析了药丸经历的力和扭矩范围的时间分数,并与胃消化的生理阶段相关。我们还报告了体内药丸经历的最大力和扭矩,作为肌肉收缩导致胃排空期间药丸经历的力的定量测量。从人体数据计算出的结果与具有转化研究重点的小型和大型动物模型进行了比较。健康胃中药丸经历的胃力的报告幅度和方向可用作与病理生理状态进行比较的基线。具有临床意义的是,力矢量数据的方向性可能有助于确定与胃肠道动力障碍相关的肌肉群。此外,人体和动物模型之间的定量比较可以深入了解比较性胃收缩性,从而有助于合理的药丸设计,并为解释胃滞留口服制剂测试结果提供定量框架。